Next Issue
Previous Issue

Table of Contents

Biomedicines, Volume 6, Issue 1 (March 2018)

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
Cover Story (view full-size image) Single nucleotide polymorphisms (SNPs) in GJA4 (the gene that codes for Cx37) have previously been [...] Read more.
View options order results:
result details:
Displaying articles 1-36
Export citation of selected articles as:
Open AccessReview The Direct and Indirect Roles of NF-κB in Cancer: Lessons from Oncogenic Fusion Proteins and Knock-in Mice
Biomedicines 2018, 6(1), 36; https://doi.org/10.3390/biomedicines6010036
Received: 28 February 2018 / Revised: 16 March 2018 / Accepted: 17 March 2018 / Published: 19 March 2018
Cited by 1 | PDF Full-text (1742 KB) | HTML Full-text | XML Full-text | Correction
Abstract
NF-κB signaling pathways play an important role in the regulation of cellular immune and stress responses. Aberrant NF-κB activity has been implicated in almost all the steps of cancer development and many of the direct and indirect contributions of this transcription factor system
[...] Read more.
NF-κB signaling pathways play an important role in the regulation of cellular immune and stress responses. Aberrant NF-κB activity has been implicated in almost all the steps of cancer development and many of the direct and indirect contributions of this transcription factor system for oncogenesis were revealed in the recent years. The indirect contributions affect almost all hallmarks and enabling characteristics of cancer, but NF-κB can either promote or antagonize these tumor-supportive functions, thus prohibiting global NF-κB inhibition. The direct effects are due to mutations of members of the NF-κB system itself. These mutations typically occur in upstream components that lead to the activation of NF-κB together with further oncogenesis-promoting signaling pathways. In contrast, mutations of the downstream components, such as the DNA-binding subunits, contribute to oncogenic transformation by affecting NF-κB-driven transcriptional output programs. Here, we discuss the features of recently identified oncogenic RelA fusion proteins and the characterization of pathways that are regulating the transcriptional activity of NF-κB by regulatory phosphorylations. As NF-κB’s central role in human physiology prohibits its global inhibition, these auxiliary or cell type-specific NF-κB regulating pathways are potential therapeutic targets. Full article
(This article belongs to the Special Issue Roles of NF-kB in Cancer and Their Therapeutic Approaches)
Figures

Graphical abstract

Open AccessReview VHL and Hypoxia Signaling: Beyond HIF in Cancer
Biomedicines 2018, 6(1), 35; https://doi.org/10.3390/biomedicines6010035
Received: 24 February 2018 / Revised: 12 March 2018 / Accepted: 16 March 2018 / Published: 19 March 2018
PDF Full-text (609 KB) | HTML Full-text | XML Full-text
Abstract
Von Hippel-Lindau (VHL) is an important tumor suppressor that is lost in the majority of clear cell carcinoma of renal cancer (ccRCC). Its regulatory pathway involves the activity of E3 ligase, which targets hypoxia inducible factor α (including HIF1α and HIF2α) for proteasome
[...] Read more.
Von Hippel-Lindau (VHL) is an important tumor suppressor that is lost in the majority of clear cell carcinoma of renal cancer (ccRCC). Its regulatory pathway involves the activity of E3 ligase, which targets hypoxia inducible factor α (including HIF1α and HIF2α) for proteasome degradation. In recent years, emerging literature suggests that VHL also possesses other HIF-independent functions. This review will focus on VHL-mediated signaling pathways involving the latest identified substrates/binding partners, including N-Myc downstream-regulated gene 3 (NDRG3), AKT, and G9a, etc., and their physiological roles in hypoxia signaling and cancer. We will also discuss the crosstalk between VHL and NF-κB signaling. Lastly, we will review the latest findings on targeting VHL signaling in cancer. Full article
(This article belongs to the Special Issue Hypoxia)
Figures

Graphical abstract

Open AccessConference Report Update in Systemic and Targeted Therapies in Gastrointestinal Oncology
Biomedicines 2018, 6(1), 34; https://doi.org/10.3390/biomedicines6010034
Received: 1 January 2018 / Revised: 28 February 2018 / Accepted: 6 March 2018 / Published: 16 March 2018
PDF Full-text (243 KB) | HTML Full-text | XML Full-text
Abstract
Progress has been made in the treatment of gastrointestinal cancers through advances in systemic therapies, surgical interventions, and radiation therapy. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference, the faculty members of the Penn State Health Milton S. Hershey Medical Center presented
[...] Read more.
Progress has been made in the treatment of gastrointestinal cancers through advances in systemic therapies, surgical interventions, and radiation therapy. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference, the faculty members of the Penn State Health Milton S. Hershey Medical Center presented a variety of topics that focused on this sub-specialty. This conference paper highlights the new development in systemic treatment of various malignant diseases in the digestive system. Results of the recent clinical trials that investigated the clinical efficacy of pegylated hyaluronidase, napabucasin, and L-asparaginase in pancreatic carcinoma are presented. The use of peri-operative chemotherapy comprised of 5-fluorouracil or capecitabine, leucovorin, oxaliplatin, and docetaxel (FLOT), and immunotherapy including pembrolizumab, nivolumab, and ipilimumab in gastroesophageal carcinoma are discussed. Data from clinical trials that investigated the targeted therapeutics including nivolumab, ramucirumab, lenvatinib, and BLU-554 are reported. The role of adjuvant capecitabine in resected biliary tract carcinoma (BTC) and nab-paclitaxel in combination with gemcitabine and cisplatin in advanced BTC are presented. In colorectal carcinoma, the efficacy of nivolumab, adjuvant FOLFOX or CAPOX, irinotecan/cetuximab/vemurafenib, and trifluridine/tipiracil/bevacizumab, is examined. In summary, some of the above systemic therapies have become or are expected to become new standard of care, while the others demonstrate the potential of becoming new treatment options. Full article
(This article belongs to the Special Issue Cancer Biomarkers and Targets in Digestive Organs)
Open AccessReview Oncolytic Adenoviruses in Gastrointestinal Cancers
Biomedicines 2018, 6(1), 33; https://doi.org/10.3390/biomedicines6010033
Received: 31 January 2018 / Revised: 5 March 2018 / Accepted: 9 March 2018 / Published: 11 March 2018
PDF Full-text (208 KB) | HTML Full-text | XML Full-text
Abstract
Gastrointestinal malignancies are challenging cancers with considerable economic and societal impacts on health care systems worldwide. While advances in surgical approaches have provided benefits to a proportion of patients, only modest improvements have been attained in the treatment of patients with advanced disease,
[...] Read more.
Gastrointestinal malignancies are challenging cancers with considerable economic and societal impacts on health care systems worldwide. While advances in surgical approaches have provided benefits to a proportion of patients, only modest improvements have been attained in the treatment of patients with advanced disease, resulting in limited improvement in survival rates in these patients. Oncolytic adenoviruses are being developed to address gastrointestinal malignancies. Each platform has evolved to maximize tumor-cell killing potency while minimizing toxicities. Tumor-specific bioengineered adenoviruses using chimeric promoters, prodrug convertase enzymes, lethal genes, tumor suppressor genes, and pseudo-typed capsids can provide the innovations for eventual success of oncolytic virotherapy. This article will review the developments in adenoviral platforms in the context of specific gastrointestinal cancers. From the bench to the implementation of clinical trials, this review aims to highlight advances in the field from its early days to the current state of affairs as it pertains to the application of adenoviral oncolytic therapy to gastrointestinal cancers. Full article
(This article belongs to the Special Issue Adenoviruses: From Virus to Medicine)
Figures

Graphical abstract

Open AccessReview Molecular Characterization of Gastric Carcinoma: Therapeutic Implications for Biomarkers and Targets
Biomedicines 2018, 6(1), 32; https://doi.org/10.3390/biomedicines6010032
Received: 1 January 2018 / Revised: 11 February 2018 / Accepted: 5 March 2018 / Published: 9 March 2018
PDF Full-text (805 KB) | HTML Full-text | XML Full-text
Abstract
Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC). Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker
[...] Read more.
Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC). Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2) amplification and programmed death-ligand 1 (PD-L1) expression for effectiveness of trastuzumab and pembrolizumab, respectively. Multi-platform molecular analysis of cancer, including GC, may help identify predictive biomarkers to guide selection of therapeutic agents. Molecular classification of GC by The Cancer Genome Atlas Research Network and the Asian Cancer Research Group is expected to identify therapeutic targets and predictive biomarkers. Complementary to molecular characterization of GC is molecular profiling by expression analysis and genomic sequencing of tumor DNA. Initial analysis of patients with gastroesophageal carcinoma demonstrates that the ratio of progression-free survival (PFS) on molecular profile (MP)-based treatment to PFS on treatment prior to molecular profiling exceeds 1.3, suggesting the potential value of MP in guiding selection of individualized therapy. Future strategies aiming to integrate molecular classification and profiling of tumors with therapeutic agents for achieving the goal of personalized treatment of GC are indicated. Full article
(This article belongs to the Special Issue Cancer Biomarkers and Targets in Digestive Organs)
Figures

Graphical abstract

Open AccessReview CD117/c-kit in Cancer Stem Cell-Mediated Progression and Therapeutic Resistance
Biomedicines 2018, 6(1), 31; https://doi.org/10.3390/biomedicines6010031
Received: 2 February 2018 / Revised: 28 February 2018 / Accepted: 5 March 2018 / Published: 8 March 2018
PDF Full-text (1413 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Metastasis is the primary cause of cancer patient morbidity and mortality, but due to persisting gaps in our knowledge, it remains untreatable. Metastases often occur as patient tumors progress or recur after initial therapy. Tumor recurrence at the primary site may be driven
[...] Read more.
Metastasis is the primary cause of cancer patient morbidity and mortality, but due to persisting gaps in our knowledge, it remains untreatable. Metastases often occur as patient tumors progress or recur after initial therapy. Tumor recurrence at the primary site may be driven by a cancer stem-like cell or tumor progenitor cell, while recurrence at a secondary site is driven by metastatic cancer stem cells or metastasis-initiating cells. Ongoing efforts are aimed at identifying and characterizing these stem-like cells driving recurrence and metastasis. One potential marker for the cancer stem-like cell subpopulation is CD117/c-kit, a tyrosine kinase receptor associated with cancer progression and normal stem cell maintenance. Further, activation of CD117 by its ligand stem cell factor (SCF; kit ligand) in the progenitor cell niche stimulates several signaling pathways driving proliferation, survival, and migration. This review examines evidence that the SCF/CD117 signaling axis may contribute to the control of cancer progression through the regulation of stemness and resistance to tyrosine kinase inhibitors. Full article
(This article belongs to the Special Issue Stem Cells and Cancer Therapeutics)
Figures

Graphical abstract

Open AccessReview The Repertoire of Adenovirus in Human Disease: The Innocuous to the Deadly
Biomedicines 2018, 6(1), 30; https://doi.org/10.3390/biomedicines6010030
Received: 27 January 2018 / Revised: 26 February 2018 / Accepted: 1 March 2018 / Published: 7 March 2018
PDF Full-text (234 KB) | HTML Full-text | XML Full-text
Abstract
Adenoviridae is a family of double-stranded DNA viruses that are a significant cause of upper respiratory tract infections in children and adults. Less commonly, the adenovirus family can cause a variety of gastrointestinal, ophthalmologic, genitourinary, and neurologic diseases. Most adenovirus infections are self-limited
[...] Read more.
Adenoviridae is a family of double-stranded DNA viruses that are a significant cause of upper respiratory tract infections in children and adults. Less commonly, the adenovirus family can cause a variety of gastrointestinal, ophthalmologic, genitourinary, and neurologic diseases. Most adenovirus infections are self-limited in the immunocompetent host and are treated with supportive measures. Fatal infections can occur in immunocompromised patients and less frequently in the healthy. Adenoviral vectors are being studied for novel biomedical applications including gene therapy and immunization. In this review we will focus on the spectrum of adenoviral infections in humans. Full article
(This article belongs to the Special Issue Adenoviruses: From Virus to Medicine)
Figures

Graphical abstract

Open AccessReview Role of Akt Isoforms Controlling Cancer Stem Cell Survival, Phenotype and Self-Renewal
Biomedicines 2018, 6(1), 29; https://doi.org/10.3390/biomedicines6010029
Received: 31 January 2018 / Revised: 23 February 2018 / Accepted: 6 March 2018 / Published: 7 March 2018
Cited by 1 | PDF Full-text (514 KB) | HTML Full-text | XML Full-text
Abstract
The cancer stem cell (CSC) hypothesis suggests that tumours are maintained by a subpopulation of cells with stem cell properties. Although the existence of CSCs was initially described in human leukaemia, less evidence exists for CSCs in solid tumours. Recently, a CD133+ cell
[...] Read more.
The cancer stem cell (CSC) hypothesis suggests that tumours are maintained by a subpopulation of cells with stem cell properties. Although the existence of CSCs was initially described in human leukaemia, less evidence exists for CSCs in solid tumours. Recently, a CD133+ cell subpopulation was isolated from human brain tumours exhibiting stem cell properties in vitro as well as the capacity to initiate tumours in vivo. In the present work, we try to summarize the data showing that some elements of the Phosphoinositide 3-kinase Class I (PI3K)/ Thymoma viral oncogene protein kinase (Akt) pathway, such the activity of PI3K Class I or Akt2, are necessary to maintain the CSC-like phenotype as well as survival of CSCs (also denoted as tumour-initiating cells (TICs)). Our data and other laboratory data permit a working hypothesis in which each Akt isoform plays an important and specific role in CSC/TIC growth, self-renewal, maintaining survival, and epithelial-mesenchymal transition (EMT) phenotype, not only in breast cancer, but also in glioma. We suggest that a more complete understanding is needed of the possible roles of isoforms in human tumours (iso-signalling determination). Thus, a comprehensive analysis of how hierarchical signalling is assembled during oncogenesis, how cancer landmarks are interconnected to favour CSC and tumour growth, and how some protein isoforms play a specific role in CSCs to ensure that survival and proliferation must be done in order to propose/generate new therapeutic approaches (alone or in combination with existing ones) to use against cancer. Full article
(This article belongs to the Special Issue Stem Cells and Cancer Therapeutics)
Figures

Graphical abstract

Open AccessReview Updates in the Development of ImmunoRNases for the Selective Killing of Tumor Cells
Biomedicines 2018, 6(1), 28; https://doi.org/10.3390/biomedicines6010028
Received: 8 February 2018 / Revised: 2 March 2018 / Accepted: 3 March 2018 / Published: 5 March 2018
Cited by 1 | PDF Full-text (519 KB) | HTML Full-text | XML Full-text
Abstract
Targeted cancer therapy includes, amongst others, antibody-based delivery of toxic payloads to selectively eliminate tumor cells. This payload can be either a synthetic small molecule drug composing an antibody-drug conjugate (ADC) or a cytotoxic protein composing an immunotoxin (IT). Non-human cytotoxic proteins, while
[...] Read more.
Targeted cancer therapy includes, amongst others, antibody-based delivery of toxic payloads to selectively eliminate tumor cells. This payload can be either a synthetic small molecule drug composing an antibody-drug conjugate (ADC) or a cytotoxic protein composing an immunotoxin (IT). Non-human cytotoxic proteins, while potent, have limited clinical efficacy due to their immunogenicity and potential off-target toxicity. Humanization of the cytotoxic payload is essential and requires harnessing of potent apoptosis-inducing human proteins with conditional activity, which rely on targeted delivery to contact their substrate. Ribonucleases are attractive candidates, due to their ability to induce apoptosis by abrogating protein biosynthesis via tRNA degradation. In fact, several RNases of the pancreatic RNase A superfamily have shown potential as anti-cancer agents. Coupling of a human RNase to a humanized antibody or antibody derivative putatively eliminates the immunogenicity of an IT (now known as a human cytolytic fusion protein, hCFP). However, RNases are tightly regulated in vivo by endogenous inhibitors, controlling the ribonucleolytic balance subject to the cell’s metabolic requirements. Endogenous inhibition limits the efficacy with which RNase-based hCFPs induce apoptosis. However, abrogating the natural interaction with the natural inhibitors by mutation has been shown to significantly enhance RNase activity, paving the way toward achieving cytolytic potency comparable to that of bacterial immunotoxins. Here, we review the immunoRNases that have undergone preclinical studies as anti-cancer therapeutic agents. Full article
(This article belongs to the Special Issue Immuno-Active Cancer Therapeutics)
Figures

Graphical abstract

Open AccessReview The Application of Gene Expression Profiling in Predictions of Occult Lymph Node Metastasis in Colorectal Cancer Patients
Biomedicines 2018, 6(1), 27; https://doi.org/10.3390/biomedicines6010027
Received: 31 December 2017 / Revised: 24 February 2018 / Accepted: 1 March 2018 / Published: 2 March 2018
PDF Full-text (206 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A key factor in determining the likely outcome for a patient with colorectal cancer is whether or not the tumour has metastasised to the lymph nodes—information which is also important in assessing any possibilities of lymph node resection so as to improve survival.
[...] Read more.
A key factor in determining the likely outcome for a patient with colorectal cancer is whether or not the tumour has metastasised to the lymph nodes—information which is also important in assessing any possibilities of lymph node resection so as to improve survival. In this review we perform a wide-range assessment of literature relating to recent developments in gene expression profiling (GEP) of the primary tumour, to determine their utility in assessing node status. A set of characteristic genes seems to be involved in the prediction of lymph node metastasis (LNM) in colorectal patients. Hence, GEP is applicable in personalised/individualised/tailored therapies and provides insights into developing novel therapeutic targets. Not only is GEP useful in prediction of LNM, but it also allows classification based on differences such as sample size, target gene expression, and examination method. Full article
Figures

Graphical abstract

Open AccessFeature PaperReview Immune Monitoring of Cancer Patients Prior to and During CTLA-4 or PD-1/PD-L1 Inhibitor Treatment
Biomedicines 2018, 6(1), 26; https://doi.org/10.3390/biomedicines6010026
Received: 29 January 2018 / Revised: 19 February 2018 / Accepted: 23 February 2018 / Published: 1 March 2018
PDF Full-text (3528 KB) | HTML Full-text | XML Full-text
Abstract
Targeting the immune checkpoint receptors cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death 1 ligand 1 (PD-L1) represents a very attractive treatment modality for tumor patients. The administration of antibodies against these receptors can promote
[...] Read more.
Targeting the immune checkpoint receptors cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death 1 ligand 1 (PD-L1) represents a very attractive treatment modality for tumor patients. The administration of antibodies against these receptors can promote efficient antitumor effects and can induce objective clinical responses in about 20–40% patients with various tumor types, accompanied by improved survival. Based on their therapeutic efficiency, several antibodies have been approved for the treatment of tumor patients. However, many patients do not respond to checkpoint inhibitor therapy. Therefore, the identification of biomarkers is required to guide patient selection for this treatment modality. Here, we summarize recent studies investigating the PD-L1 expression or mutational load of tumor tissues as well as the frequency and phenotype of immune cells in tumor patients prior to and during CTLA-4 or PD-1/PD-L1 inhibitor treatment. Full article
(This article belongs to the Special Issue Dissecting the Immunological Landscape of Human Malignancies)
Figures

Graphical abstract

Open AccessReview The Peripheral and Intratumoral Immune Cell Landscape in Cancer Patients: A Proxy for Tumor Biology and a Tool for Outcome Prediction
Biomedicines 2018, 6(1), 25; https://doi.org/10.3390/biomedicines6010025
Received: 26 January 2018 / Revised: 18 February 2018 / Accepted: 22 February 2018 / Published: 24 February 2018
PDF Full-text (928 KB) | HTML Full-text | XML Full-text
Abstract
Functional systemic and local immunity is required for effective anti-tumor responses. In addition to an active engagement with cancer cells and tumor stroma, immune cells can be affected and are often found to be dysregulated in cancer patients. The impact of tumors on
[...] Read more.
Functional systemic and local immunity is required for effective anti-tumor responses. In addition to an active engagement with cancer cells and tumor stroma, immune cells can be affected and are often found to be dysregulated in cancer patients. The impact of tumors on local and systemic immunity can be assessed using a variety of approaches ranging from low-dimensional analyses that are performed on large patient cohorts to multi-dimensional assays that are technically and logistically challenging and are therefore confined to a limited sample size. Many of these strategies have been established in recent years leading to exciting findings. Not only were analyses of immune cells in tumor patients able to predict the clinical course of the disease and patients’ survival, numerous studies also detected changes in the immune landscape that correlated with responses to novel immunotherapies. This review will provide an overview of established and novel tools for assessing immune cells in tumor patients and will discuss exemplary studies that utilized these techniques to predict patient outcomes. Full article
(This article belongs to the Special Issue Dissecting the Immunological Landscape of Human Malignancies)
Figures

Figure 1

Open AccessArticle Carcinoembryonic Antigen Serum Levels in Nonmelanoma Skin Cancer
Biomedicines 2018, 6(1), 24; https://doi.org/10.3390/biomedicines6010024
Received: 6 January 2018 / Revised: 21 February 2018 / Accepted: 21 February 2018 / Published: 23 February 2018
PDF Full-text (536 KB) | HTML Full-text | XML Full-text
Abstract
Background: Carcinoembryonic antigen (CEA) is a glycoprotein, which is present in the foetal colon, some benign conditions and different malignancies, particularly in colon adenocarcinoma. We focused this study on non-melanoma skin cancer (NMSC). NMSC is a common malignancy and it is an important
[...] Read more.
Background: Carcinoembryonic antigen (CEA) is a glycoprotein, which is present in the foetal colon, some benign conditions and different malignancies, particularly in colon adenocarcinoma. We focused this study on non-melanoma skin cancer (NMSC). NMSC is a common malignancy and it is an important source of morbidity and death in the world. In this study we evaluated whether CEA level increases in NMSC. Patients and Methods: A total of 566 patients with non-melanoma skin cancer (NMSC) were enrolled; 286 patients with NMSC showed CEA levels above normal values, and 280 showed CEA levels below normal values. Patients with high levels of CEA underwent abdominal ultrasound, gastro endoscopy, colonoscopy, and abdominal CT scans. Results: We studied 566 patients, 286 were positive to CEA and 280 were negative. Of the 286 patients positive to CEA, 132 had basal cell carcinoma (64 patients had an associated cancer) and 154 had squamous cell carcinoma (75 patients were affected by cancer). Of the 280 patients negative to CEA, 130 had basal cell carcinoma (12 were associated with cancer), and 150 had squamous cell carcinoma (18 were associated with cancer). The mean age of the 566 case control subjects were 65–81 years. Of the 10 subjects that were the positive control for CEA, two had cancer. Of the 556 subjects that were the negative control for CEA, three had cancer. Conclusions: In patients that present high serum levels of CEA, we give attention to adenocarcinoma tumour first. The pattern of association may be attributable to bias because the group with NMSC were frequently evaluated than those with no history of NMSC. Our results showed that out of 286 patients that were CEA-positive, 139 had cancer, and of the 280 that were CEA-negative, 30 had cancer. Therefore, 20% of patients do not follow the trend. Other markers should be investigated. Full article
Figures

Graphical abstract

Open AccessArticle GJA4/Connexin 37 Mutations Correlate with Secondary Lymphedema Following Surgery in Breast Cancer Patients
Biomedicines 2018, 6(1), 23; https://doi.org/10.3390/biomedicines6010023
Received: 31 December 2017 / Revised: 1 February 2018 / Accepted: 13 February 2018 / Published: 22 February 2018
Cited by 1 | PDF Full-text (1130 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Lymphedema is a condition resulting from mutations in various genes essential for lymphatic development and function, which leads to obstruction of the lymphatic system. Secondary lymphedema is a progressive and incurable condition, most often manifesting after surgery for breast cancer. Although its causation
[...] Read more.
Lymphedema is a condition resulting from mutations in various genes essential for lymphatic development and function, which leads to obstruction of the lymphatic system. Secondary lymphedema is a progressive and incurable condition, most often manifesting after surgery for breast cancer. Although its causation appears complex, various lines of evidence indicate that genetic predisposition may play a role. Previous studies show that mutations in connexin 47 are associated with secondary lymphedema. We have tested the hypothesis that connexin 37 gene mutations in humans are associated with secondary lymphedema following breast cancer surgery. A total of 2211 breast cancer patients were screened and tested for reference single nucleotide polymorphisms (SNPs) of the GJA4 gene (gap junction protein alpha 4 gene). The results presented in this paper indicate that two SNPs in the 3’ UTR (the three prime untranslated region) of the GJA4 gene are associated with an increased risk of secondary lymphedema in patients undergoing breast cancer treatment. Our results provide evidence of a novel genetic biomarker for assessing the predisposition to secondary lymphedema in human breast cancer patients. Testing for the condition-associated alleles described here could assist and inform treatment and post-operative care plans of breast cancer patients, with potentially positive outcomes for the management of disease progression. Full article
Figures

Graphical abstract

Open AccessReview Targeting Leukemia Stem Cells in the Bone Marrow Niche
Biomedicines 2018, 6(1), 22; https://doi.org/10.3390/biomedicines6010022
Received: 8 January 2018 / Revised: 6 February 2018 / Accepted: 17 February 2018 / Published: 21 February 2018
PDF Full-text (698 KB) | HTML Full-text | XML Full-text
Abstract
The bone marrow (BM) niche encompasses multiple cells of mesenchymal and hematopoietic origin and represents a unique microenvironment that is poised to maintain hematopoietic stem cells. In addition to its role as a primary lymphoid organ through the support of lymphoid development, the
[...] Read more.
The bone marrow (BM) niche encompasses multiple cells of mesenchymal and hematopoietic origin and represents a unique microenvironment that is poised to maintain hematopoietic stem cells. In addition to its role as a primary lymphoid organ through the support of lymphoid development, the BM hosts various mature lymphoid cell types, including naïve T cells, memory T cells and plasma cells, as well as mature myeloid elements such as monocyte/macrophages and neutrophils, all of which are crucially important to control leukemia initiation and progression. The BM niche provides an attractive milieu for tumor cell colonization given its ability to provide signals which accelerate tumor cell proliferation and facilitate tumor cell survival. Cancer stem cells (CSCs) share phenotypic and functional features with normal counterparts from the tissue of origin of the tumor and can self-renew, differentiate and initiate tumor formation. CSCs possess a distinct immunological profile compared with the bulk population of tumor cells and have evolved complex strategies to suppress immune responses through multiple mechanisms, including the release of soluble factors and the over-expression of molecules implicated in cancer immune evasion. This chapter discusses the latest advancements in understanding of the immunological BM niche and highlights current and future immunotherapeutic strategies to target leukemia CSCs and overcome therapeutic resistance in the clinic. Full article
(This article belongs to the Special Issue Stem Cells and Cancer Therapeutics)
Figures

Graphical abstract

Back to Top